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Guidance for a personal target value of FeNO in allergic asthma: Case report and theoretical example.
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PMID:  22793785     Owner:  NLM     Status:  Publisher    
Abstract In clinically stable asthma the exhaled NO values (F(E)NO) are generally higher than in control subjects. Therefore, reference values are of limited importance in clinical practice. This is demonstrated in this case report, but it is also shown that NO parameters from non-linear modelling do have a clinical value. A subject with asthma was treated with inhaled corticosteroids for 1 week. The non-linear NO model was used to measure the response to treatment. The NO parameters from subjects with atopic rhinitis and asthma were fed into a computer program to generate theoretical F(E)NO(0.05) values, i.e. target values. There was a dramatic decrease in F(E)NO(0.05) due to treatment, from 82 to 34 ppb, but it remained higher than in healthy controls. This is due to the elevated diffusion rate of NO, unchanged by treatment. When the NO parameters are known, a personal best value of F(E)NO(0.05) (fractional concentration of exhaled NO in the gas phase, 0.05 L/s) can be calculated, which can be the target value when only F(E)NO(0.05) can be monitored. In conclusion, reference values for NO parameters are shown to be clinically useful. It is essential that every patient receives his/her target value of F(E)NO(0.05), when only a single NO measurement is available. In our opinion, this is the reason why there are few successful studies of trying to target the NO value with inhaled corticosteroids.
Marieann Högman; Pekka Meriläinen
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-7-16
Journal Detail:
Title:  Upsala journal of medical sciences     Volume:  -     ISSN:  2000-1967     ISO Abbreviation:  -     Publication Date:  2012 Jul 
Date Detail:
Created Date:  2012-7-16     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0332203     Medline TA:  Ups J Med Sci     Country:  -    
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Languages:  ENG     Pagination:  -     Citation Subset:  -    
Department of Medical Sciences, Respiratory Medicine and Allergology, Uppsala University , Uppsala , Sweden.
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Journal Information
Journal ID (nlm-ta): Ups J Med Sci
Journal ID (iso-abbrev): Ups. J. Med. Sci
Journal ID (publisher-id): UPS
ISSN: 0300-9734
ISSN: 2000-1967
Publisher: Informa Healthcare
Article Information
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© Informa Healthcare
Received Day: 10 Month: 4 Year: 2012
Accepted Day: 14 Month: 6 Year: 2012
Print publication date: Month: 3 Year: 2013
Electronic publication date: Day: 13 Month: 2 Year: 2013
Volume: 118 Issue: 1
First Page: 59 Last Page: 61
PubMed Id: 22793785
ID: 3572674
DOI: 10.3109/03009734.2012.704433
Publisher Id: UPS_A_704433_O

Guidance for a personal target value of FENO in allergic asthma: Case report and theoretical example
Marieann Högman12
Pekka Meriläinen1
1Department of Medical Sciences, Respiratory Medicine and Allergology, Uppsala University, Uppsala, Sweden
2Centre for Research and Development, Uppsala University/County Council of Gävleborg, Gävle, Sweden
Correspondence: Correspondence: Marieann Högman, Centre for Research and Development, Uppsala University/County Council of Gävleborg, SE 801 88 Gävle, Sweden.


Studies have been designed to use exhaled NO to target the treatment of asthma, and recently a Cochrane review has concluded that, at present, defining the dose of inhaled corticosteroids based on exhaled NO cannot be routinely advocated (1). It has also been concluded in an American Thoracic Society/European Respiratory Society (ATS/ERS) document on standardizing end-points for clinical asthma trials and clinical practice that in clinically stable asthma the exhaled NO (FENO) values are generally higher than in healthy control subjects (2). Therefore, reference NO values are of limited use in guiding the clinician in the treatment of patients with asthma. In the present case study it is demonstrated why the FENO0.05 (fractional concentration of exhaled NO in the gas phase, 0.05 L/s) remains high after treatment and that NO parameters from non-linear modelling are clinically useful.

Case study

A male subject, 30 years of age, with the diagnosis of atopic asthma since childhood was investigated. The baseline NO analysis was done without inhaled corticosteroids (ICS). After one week on 800 microgram ICS twice a day, FENO values were obtained again with multiple flow rates using a CLD 88sp NO analyser (ECO Medics AG, Switzerland). The NO production of the respiratory system was computed with the non-linear NO model by Högman and Meriläinen (3).

There was a dramatic decrease in FENO0.05 of 58% in 1 week of treatment, but it was still higher than reference values for healthy controls (4). In Figure 1 it can be seen that there was no change in airway diffusion capacity of NO (DawNO) due to ICS. DawNO is known to be increased in atopic rhinitis and atopic asthma (5) and not affected by ICS (6). The alveolar NO levels (CANO) were low. Noteworthily, the airway tissue content (CawNO) was reduced by ICS to levels presented for healthy controls (4).

Theoretical example

When the NO parameters are known, the non-linear model can be used to calculate the FENO0.05 (3). Different values of CawNO, DawNO, and CANO can be fed into a Microsoft Office Excel spreadsheet, where NO volumes at different expiratory flow rates are visualized and FENO for specific flow rates are given. For the illustration, typical NO values in health, atopy, and asthma are shown in Table I. Since DawNO is not affected by ICS, this value can be used in the calculations together with CawNO and CANO values for healthy controls (3). This calculation will result in a personal best or target value of FENO0.05 to be used during treatment. This target value of FENO0.05 was quite similar to the value after 1 week of treatment in this case study and in a group of asthmatics in a study by Silkoff et al. (6).


One week of ICS reduced the CawNO to reference levels for healthy controls. The FENO0.05 level stayed elevated, which is due to the lack of change in DawNO, known to be high in allergic asthma (5) and not affected by ICS in asthma (6).

In a study by Smith et al. (7) it was concluded that optimum FENO levels were best established by using oral rather than inhaled steroid treatment and that values were higher than reference values even though asthma was well controlled. The finding in this case study gives other solutions to finding the personal best value of FENO0.05. One solution is to use the non-linear NO model and follow the ICS treatment with CawNO. Another solution is to determine the DawNO for the patient and then use the CawNO and CANO for healthy controls to identify a target value of FENO0.05. In our patient it was 33 ppb. The FENO value can then be followed with a simple portable NO device in primary care.

The importance of controlling FENO has been shown in children, where airway hyper-responsiveness improved with lower FENO (8), and in difficult-to-treat asthma, where an increased NO value was a predictor of accelerated decline in lung function (9). Therefore NO values should preferentially be monitored in allergic asthma in both children and adults, and DawNO is useful for targeting FENO0.05. Further studies have to be designed to evaluate the personal best NO value by an approach presented in this case report.

Declaration of interest: The authors report no conflict of interest. The authors alone are responsible for the content and writing of the paper.

1.. Petsky HL,Cates CJ,Li A,Kynaston JA,Turner C,Chang AB. Tailored interventions based on exhaled nitric oxide versus clinical symptoms for asthma in children and adultsCochrane Database Syst RevYear: 2009CD00634019821360
2.. Reddel HK,Taylor DR,Bateman ED,Boulet LP,Boushey HA,Busse WW,et al. An official American Thoracic Society/European Respiratory Society statement: asthma control and exacerbations: standardizing endpoints for clinical asthma trials and clinical practiceAm J Respir Crit Care MedYear: 2009180599919535666
3.. Högman M,Meriläinen P. Extended NO analysis in asthmaJ Breath ResYear: 2007102400121383432
4.. Högman M,Lafih J,Meriläinen P,Bröms K,Malinovschi A,Janson C. Extended NO analysis in a healthy subgroup of a random sample from a Swedish populationClin Physiol Funct ImagingYear: 200929182318803639
5.. Högman M,Holmkvist T,Wegener T,Emtner M,Andersson M,Hedenström H,et al. Extended NO analysis applied to patients with COPD, allergic asthma and allergic rhinitisRespir MedYear: 200296243011863206
6.. Silkoff PE,Sylvester JT,Zamel N,Permutt S. Airway nitric oxide diffusion in asthma. Role in pulmonary function and bronchial responsivenessAm J Respir Crit Care MedYear: 200016112182810764315
7.. Smith AD,Cowan JO,Taylor DR. Exhaled nitric oxide levels in asthma: personal best versus reference valuesJ Allergy Clin ImmunolYear: 20091247141819767074
8.. Pijnenburg MW,Bakker EM,Hop WC,de Jongste JC. Titrating steroids on exhaled nitric oxide in children with asthma: a randomized controlled trialAm J Respir Crit Care MedYear: 2005172831615976380
9.. van Veen IH,Ten Brinke A,Sterk PJ,Sont JK,Gauw SA,Rabe KF,et al. Exhaled nitric oxide predicts lung function decline in difficult-to-treat asthmaEur Respir JYear: 200832344918508818


[Figure ID: F1]
Figure 1. 

FENO0.05 and NO parameters, airway tissue concentration of NO (CawNO), airway diffusion capacity for NO (DawNO), and alveolar levels of NO (CANO) in a case of allergic asthma. Values are given before and after 1 week of inhaled corticosteroids. Reference values for healthy controls are marked with a broken line (Högman et al. (4)). Note the decline in CawNO to reference values while FENO0.05 remained high.

[TableWrap ID: T1] Table I. 

CANO, CawNO, DawNO, and FENO0.05 values in health, atopy, and asthma. During steroid treatment, the target value of FENO0.05 can be calculated when the DawNO is known.

Theoretical example CANO (ppb) CawNO (ppb) DawNO (mL/s) FENO0.05 (ppb) Ref.
Healthy subject 1 106 8 16 (4)
Atopic rhinitis 1 106 12 23 (5)
 Target FENO0.05 23
Atopic asthma
Before steroids 1 266 18 82 This case report
After steroids 1 102 20 34
 Target FENO0.05 33
At 6 weeks withdrawal of steroids 3 255 25 102 Adopted from (6)
After steroids 3 108 22 40
 Target FENO0.05 42

CANO = calculated fractional concentration of NO in the gas phase of the alveolar region; CawNO = calculated tissue concentration of NO of the airway wall; DawNO = calculated airway compartment diffusing-capacity from the airway wall to the gas stream; FENO0.05 = fractional concentration of exhaled NO in the gas phase 0.05 L/s.

Article Categories:
  • Case Report

Keywords: Asthma, nitric oxide, treatment.

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